ArticleMolecular cancer2022
An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Paclitaxel Nanomedicines: Molecular Mechanisms of Drug Resistance, Tumor Microenvironment-Responsive Delivery, and Translational Challenges.International journal of molecular sciences · 2026Review
- CDKN1A promotes paclitaxel resistance through mediating formation of polyploid giant cancer cells and enhancing neosis in non-small cell lung cancer.Translational lung cancer research · 2026Article
- Enhanced Bioactivity ofFood science & nutrition · 2026Article
- Decoding the gut microbiota-immune dialogue: from bidirectional axis to therapeutic applications.Journal of nanobiotechnology · 2026Review
- The role of KPNA3 in multiple myeloma: implications for targeting nuclear import.Apoptosis : an international journal on programmed cell death · 2026Article
- Diurnal Regulation and Gene-Specific Vulnerability of Oxidative Alcohol-Metabolizing Enzymes to Circadian Disruption.International journal of molecular sciences · 2026Article
- An H4K12la/CEBPB-AKR1C2 signaling axis modulates the mTOR pathway to regulate cisplatin resistance in lung cancer.Oncogene · 2026Article
- Targeting serine synthesis pathway to reverse paclitaxel resistance in NSCLC with combination of paclitaxel and anlotinib.Journal of experimental & clinical cancer research : CR · 2026Article
- NFYC upregulates KLF1 expression and activate LDHA to drive glycolysis and tumor growth in glioblastoma cells.Frontiers in cell and developmental biology · 2026Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Article
- EHMT2 Suppresses ARRB1 Transcription and Activates the Hedgehog Signaling to Promote Malignant Phenotype and Stem Cell Property in Oral Squamous Cell Carcinoma.Molecular biotechnology · 2025Article
- Salidroside Enhances the Sensitivity of Lung Cancer Cells to Paclitaxel by Regulating the Wnt/β-catenin Signaling Pathway.Current medical science · 2025Article
- EHMT2-mediated R-loop formation promotes the malignant progression of prostate cancer via activating Aurora B.Clinical and translational medicine · 2025Article
- The active constituent of pine needle oil, bornyl acetate, suppresses NSCLC progression by inhibiting the PI3K/AKT/ABCB1 signaling axis.Frontiers in pharmacology · 2025Article
- Nature's carriers: leveraging extracellular vesicles for targeted drug delivery.Drug delivery · 2024Review
- Cuproptosis in lung cancer: therapeutic options and prognostic models.Apoptosis : an international journal on programmed cell death · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Caspase-4 in glioma indicates deterioration and unfavorable prognosis by affecting tumor cell proliferation and immune cell recruitment.Scientific reports · 2024Article
- Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects.Journal of pharmaceutical analysis · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer is a kind of malignancy with high morbidity and mortality worldwide. Paclitaxel (PTX) is the main treatment for non-small cell lung cancer (NSCLC), and resistance to PTX seriously affects the survival of patients. However, the underlying mechanism and potential reversing strategy need to be further explored.
methodsWe identified ALDH2 as a PTX resistance-related gene using gene microarray analysis. Subsequently, a series of functional analysis in cell lines, patient samples and xenograft models were performed to explore the functional role, clinical significance and the aberrant regulation mechanism of ALDH2 in PTX resistance of NSCLC. Furthermore, the pharmacological agents targeting ALDH2 and epigenetic enzyme were used to investigate the diverse reversing strategy against PTX resistance.
resultsUpregulation of ALDH2 expression is highly associated with resistance to PTX using in vitro and in vivo analyses of NSCLC cells along with clinicopathological analyses of NSCLC patients. ALDH2-overexpressing NSCLC cells exhibited significantly reduced PTX sensitivity and increased biological characteristics of malignancy in vitro and tumor growth and metastasis in vivo. EHMT2 (euchromatic histone lysine methyltransferase 2) inhibition and NFYA (nuclear transcription factor Y subunit alpha) overexpression had a cooperative effect on the regulation of ALDH2. Mechanistically, ALDH2 overexpression activated the RAS/RAF oncogenic pathway. NSCLC/PTX cells re-acquired sensitivity to PTX in vivo and in vitro when ALDH2 was inhibited by pharmacological agents, including the ALDH2 inhibitors Daidzin (DZN)/Disulfiram (DSF) and JIB04, which reverses the effect of EHMT2.
conclusionOur findings suggest that ALDH2 status can help predict patient response to PTX therapy and ALDH2 inhibition may be a promising strategy to overcome PTX resistance in the clinic.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.